DESCRIPTION: Chronic fatigue syndrome is a medically unexplained illness. One of the major hypotheses for its cause is immunological dysfunction. Nevertheless, no firm data exist to support the immunological hypothesis. This is likely because prior researchers have ignored the role of cytokines in producing restful sleep. Many CFS patients have disrupted sleep, and it is possible that this occurs because of an upregulated network of sleep disrupting cytokines in some patients. We propose to measure sleep disrupting cytokines (i.e., IL-4 and IL-10) and sleep producing cytokines (IL-1beta and TNF-alpha) in CFS patients on their second night in the sleep laboratory (the first night being done to deal with the well known "first night effect" and to eliminate patients with primary sleep disorders or an inability to sleep with instrumentation). In doing these studies, we are aware that there is no "gold standard" to quantify cytokines, and so we will use three different approaches - ELISA in plasma, gene message from peripheral blood monocytes (PBM) and ELISPOT to assess PBM function to immunological probes. We will study women only because CFS is predominantly an illness of women, because we want to exclude subjects with primary sleep disorders, which occur mostly in men, and because women have substantially higher levels of cytokines than men. We will compare data of CFS patients to those of healthy controls who will be as fatigued as the CFS patients because we will sleep deprive them on the night before the blood sampling night. Moreover, on the blood sampling night, we propose to match the controls to CFS patients for total sleep time. Since some CFS patients sleep without disruption, this design will provide healthy subjects sleeping without disruption and healthy subjects who sleep the same amount as those CFS patients with disrupted sleep. Finally, we will repeat this entire protocol after a day in which subjects perform a maximal exercise test because of the well-known exacerbation of CFS by exertion. We are anticipating that exercise will make some CFS patients sleep even worse than usual and exacerbate an already dysregulated cytokine sleep network.